High prevalence of human papillomavirus type 58 in patients with cervical pre-malignant lesions in southern Brazil.

Cervical cancer is the second most common type of cancer in women worldwide. Several human papillomavirus (HPV) genotypes, sexual behavior, and socioeconomic profile represent major risk factors for the development of this carcinoma. Cervical invasive cancer is preceded by cellular abnormalities that can be identified by cytological or histological exams. In order to determine the prevalence and genotypes of HPV in women with abnormal cytology or histopathology, cervical cell samples from 256 patients were evaluated for the presence of HPV/DNA by polymerase chain reaction (PCR), followed by virus genotyping by restriction fragment length polymorphism (RFLP). A total of 113 samples (51.2%) were HPV/DNA positive. Viral genotyping showed that the most prevalent genotypes were HPV 16 (34.7%) and 58 (13.8%), followed by HPV 33 (9.72%), 11 (8.33%), 18 (5.55%), 53 (5.55%), and 6 (4.2%). Four samples (5.55%) exhibited multiple infections due to the great similarity of socioeconomic characteristics and sexual behavior of HPV positive women, it was not possible to establish a risk profile for female HPV infection.

In silico analyses of a new group of fungal and plant RecQ4-homologous proteins.

Bacterial and eukaryotic RecQ helicases comprise a family of homologous proteins necessary for maintaining genomic integrity during the cell cycle and DNA repair. There is one known bacterial RecQ helicase, and five eukaryotic RecQ helicases that have been described: RecQ1p, RecQ4p, RecQ5p, Bloom, and Werner. While the biochemical functions of Bloom and Werner helicases are well understood, the same is not true for RecQ4p helicase. RecQ4p mutations lead to pathologies like Rothmund-Thompson syndrome (RTS), RAPADILINO, and Baller-Gerold syndrome (BGS). Until now, RecQ4p helicases had only been described in metazoans, and their presence in organisms like fungi and plants were not known. Thus far only one RecQ-homologous protein (Sgs1p), similar to Bloom helicase, has been described in fungal genomes. In the present study we employed an in silico approach, and successfully identified and characterized a second RecQ helicase from the genomes of different fungal and two plant species that shows similarity to metazoan RecQ4 proteins. An in-depth phylogenetic analysis of these new fungal and plant RecQ4-like sequences (termed Hrq1p) indicated that they are orthologous to the metazoan RecQ4p. We employed hydrophobic cluster analysis (HCA) and three-dimensional modeling of selected Hrq1p sequences to compare conserved regions among Hrq1p, human RecQ4p and bacterial RecQp. The results indicated that Hrq1p sequences, as previously observed for metazoan RecQ4 proteins, probably act in genomic maintenance and/or chromatin remodeling in fungal and plant cells.

Relationships among carbohydrate intermediate metabolites and DNA damage and repair in yeast from a systems biology perspective.

Glucose and fructose are major dietary carbohydrates that are essential for general metabolism. The elevated consumption of these two monosaccharides by the human population is related to the development of pluri-metabolic syndromes (e.g., diabetes mellitus and obesity). Glucose and fructose are metabolized by specific biochemical pathways to generate energy and metabolites. Many of these metabolites are mono- and bi-phosphorylated compounds, which renders them likely to generate reactive carbonyl species (RCS). Under physiological conditions, RCS react non-enzymatically with macromolecules and small molecules by means of Maillard reactions, forming stable glycated/fructated compounds called advanced glycation end products (AGEs). DNA and dNTPs are prone to react with RCS, forming DNA- and dNTP-AGEs, and many of these compounds are genotoxic and/or mutagenic. Unfortunately, little is understood about the genotoxicity and/or mutagenicity of carbohydrate intermediate metabolites or their interactions with DNA repair and carbohydrate metabolic-associated proteins. To elucidate these associations between carbohydrate metabolic pathways, DNA repair mechanisms, and dNTP-/DNA-AGEs, a systems biology study was performed by employing algorithms to mine literature data and construct physical protein-protein interactions. The results obtained in this work allow us to construct a model suggesting that yeast carbohydrate metabolic-associated enzymes activate different mechanisms for DNA repair and dNTP synthesis and act during DNA replication to protect the genome against the effects of RCS.

Aging defined by a chronologic-replicative protein network in Saccharomyces cerevisiae: an interactome analysis.

Aging is a multifactorial condition that results in the loss of an organism's fitness over time. Different theories have been formulated to explain the mechanisms of aging, but a synthesis of these theories has not been possible until now. In addition, the increase in molecular data gathered by proteomics projects utilizing different organisms has permitted a better picture of proteins that function in aging. In this sense, the yeast Saccharomyces cerevisiae is a biological model for aging, and it shows two distinct aging states: a replicative state termed the replicative lifespan (RLS) and a quiescent state known as the chronological lifespan (CLS). Interestingly, both RLS and CLS appear to share common groups of proteins, but a combined model of both aging mechanisms has not been defined. Thus, by applying systems biology tools that allow mining of the yeast proteins associated with aging, it was possible to obtain an interactome network in which both RLS and CLS are represented. In addition, four subgraphs comprising ubiquitin-dependent proteasome/regulation of cell growth, nucleic acid metabolism, carbohydrate metabolism/RNA metabolism, and carbohydrate-organic acid-amino acid/DNA metabolism were found within the interactome, defining a new model of aging for yeast termed the chronologic-replicative protein network (CRPN).